Penn Bioengineering’s Tsourkas Lab and Penn Start-up AlphaThera Awarded $667,000 SBIR Phase II Grant to Improve COVID-19 Detection Assays

To combat the COVID-19 pandemic caused by the SARS-CoV2 virus, Dr. Andrew Tsourkas’s Targeted Imaging Therapeutics and Nanomedicine (Titan) Lab in Penn Bioengineering, in collaboration with the Penn-based startup, AlphaThera, was recently awarded a $667,000 SBIR Phase II Grant Extension to support its efforts in commercializing COVID-19 detection technology. The grant supports work to address the growing need for anti-viral antibody testing. Specifically, the Tsourkas Lab and AlphaThera hope to leverage their expertise with antibody conjugation technologies to reduce the steps and complexity of existing detection assays to enable greater production and higher sensitivity tests. AlphaThera was founded in 2016 by Andrew Tsourkas, PhD, Professor of Bioengineering and James Hui, MD, PhD, a graduate of the Perelman School of Medicine and Penn Bioengineering’s doctoral program.

During this pandemic it is crucial to characterize disease prevalence among populations, understand immunity, test vaccine efficacy and monitor disease resurgence. Projections have indicated that millions of daily tests will be needed to effectively control the virus spread. One important testing method is the serological assay: These tests detect the presence of SARS-CoV2 antibodies in a person’s blood produced by the body’s immune system responding to infection. Serological tests not only diagnose active infections, but also establish prior infection in an individual, which can greatly aid in forecasting disease spread and contact tracing. To perform the serological assays for antibody detection, well-established immunoassay methods are used such as ELISA.

A variety of issues have slowed the distribution of these serological assays for antibody testing. The surge in demand for testing has caused shortages in materials and reagents that are crucial for the assays. Furthermore, complexity in some of the assay formats can slow both production and affect the sensitivity of test results. Recognizing these problems, AlphaThera is leveraging its novel conjugation technology to greatly improve upon traditional assay formats.

With AlphaThera’s conjugation technology, the orientation of antibodies can be precisely controlled so that they are aligned and uniformly immobilized on assay detection plates. This is crucial as traditional serological assays often bind antibodies to plates in a non-uniform manner, which increases variability of results and reduces sensitivity. See Fig 1 below. With AlphaThera’s uniform antibody immobilization, assay specificity could increase by as much as 1000- fold for detection of a patient’s SaRS-CoV2 antibodies.

Fig 1: Uniform vs Non-Uniform Immobilized Antibodies on Surface: Top is AlphaThera improvement, showing how antibodies would be uniformly immobilized and oriented on a plate for detection. Bottom is how many traditional serological assays immobilize antibodies, resulting in variability of results and lower specificity.

Furthermore, AlphaThera is addressing the shortage of assay reagents, specifically secondary antibody reagents, by removing certain steps from traditional serological assays. Rather than relying on secondary antibodies for detection of the patient antibodies, AlphaThera’s technology can label the patient SaRS-CoV2 primary antibodies directly in serum with a detection reagent. This eliminates several processing steps, reducing the time of the assay by as much as 50%, as well as the costs.

The Tsourkas Lab and AlphaThera have initiated their COVID-19 project, expanding into the Pennovation Center and onboarding new lab staff. Other antibody labeling products have also become available and are currently being prepared for commercialization. Check out the AlphaThera website to learn more about their technology at https://www.alphathera.com.

NIH SBIR Phase II Grant Extension— 5-R44-EB023750-03 (PI: Yu) — 10/07/2020 – 10/07/2021

July 20, 2020July 17, 2020

César de la Fuente Wins Inaugural NEMO Prize, Will Develop Rapid COVID Virus Breath Tests

The paper-based tests could be integrated directly into facemasks and provide instant results at testing sites.

When Penn Health-Tech announced its Nemirovsky Engineering and Medicine Opportunity, or NEMO Prize, in February, the center’s researchers could only begin to imagine the impact the looming COVID-19 pandemic was about to unleash. But with the promise of $80,000 to support early-stage ideas at the intersection of engineering and medicine, the contest quickly sparked a winning innovation aimed at combating the crisis.

Judges from the University of Pennsylvania’s School of Engineering and Applied Sciences and Perelman School of Medicine awarded its first NEMO Prize to César de la Fuente, PhD, who proposed a paper-based COVID diagnostic system that could capture viral particles on a person’s breath, then give a result in a matter of seconds when taken to a testing site.

Similar tests for bacteria cost less than a dollar each to make. De la Fuente, a Presidential Assistant Professor in the departments of Psychiatry, Microbiology, and Bioengineering, is aiming to make COVID tests at a similar price point and with a smaller footprint so that they could be directly integrated into facemasks, providing further incentive for their regular use.

“Wearing a facemask is vital to containing the spread of COVID because, before you know you’re sick, they block your virus-carrying droplets so those droplets can’t infect others,” de la Fuente says. “What we’re proposing could eventually lead to a mask that can be infected by the virus and let you know that you’re infected, too.”

De la Fuente’s lab has conducted molecular dynamic simulations of the regions of the SARS-COV-2 spike protein (blue) that bind to the human ACE2 receptor (red and yellow).

De la Fuente’s expertise is in synthetic biology and molecular-scale simulations of disease-causing viruses and bacteria. Having such fine-grained computational models of these microbes’ binding sites allow de la Fuente to test them against massive libraries of proteins, seeing which bind best. Other machine learning techniques can then further narrow down the minimum molecular structures responsible for binding, resulting in functional protein fragments that are easier to synthesize and manipulate.

The spike-shaped proteins that give coronaviruses their crown-like appearance and name bind to a human receptor known as ACE2. De la Fuente and his colleagues are now aiming to characterize the molecular elements and environmental factors that would allow for the most precise, reliable detection of the virus.

Read the full story on the Penn Engineering blog.

July 13, 2020July 13, 2020

Lyle Ungar: ‘Philadelphia Needs More Contact Tracers’

In May, Lyle Ungar, Professor of Computer and Information Science and Angela Duckworth, Rosa Lee and Egbert Chang Professor in Penn Arts & Sciences and the Wharton School, contributed to a New York Times op-ed on how to slow the COVID-19 pandemic through a culture of mask-wearing.

As infections continue to rise, Ungar and Duckworth are following up with another op-ed. Writing in the Philadelphia Inquirer, they outline the need to rapidly ramp-up the city and state’s contact tracing capacity:

Guidelines from health officials suggest Pennsylvania needs about 4,000 contact tracers, including 2,000 for the Philadelphia metro area. Our state has been operating with fewer than 200.

Continue reading Ungar and Duckworth’s op-ed at the Philadelphia Inquirer.

Originally posted on the Penn Engineering blog. Media contact Evan Lerner.

Lyle Ungar is a Professor of Computer and Information Science (CIS) and a member of the Penn Bioengineering Graduate Group. Read more stories about the coronavirus pandemic written by Lyle Ungar here.

June 18, 2020

Bridging the Communication Divide for Deaf and Hard-of-hearing Communities

Clear-fronted face masks, better and more frequent interpreters, and amped up involvement from local organizations have made a big difference during the COVID-19 pandemic.

By Michele Berger

Since April 23, when bioengineering alum Kate Panzer (above) and her partners at the Deaf-Hearing Communication Centre started taking orders for masks with clear fronts, they’ve shipped about 450, with a backlog of requests for hundreds more. (Image: Courtesy Kate Panzer)

Because COVID-19 spreads via respiratory droplets that disperse through sneezes and coughs, shielding the mouth and nose is an important weapon against the virus. But it can also hinder conversations for people who rely on reading lips. “Communication barriers are already difficult sometimes, and this makes it more difficult,” says linguist Jami Fisher, director of Penn’s American Sign Language (ASL)/Deaf Studies program.

It’s one of the trickiest aspects of this pandemic for those in the Deaf and hard-of-hearing communities, Fisher says. The challenge doesn’t stem just from misunderstandings due to wearing masks. It’s also about the dissemination of accurate and timely information, knowing who to rely on and how to assess what’s being said.

Trusted sources like the Swarthmore, Pennsylvania–based nonprofit Deaf-Hearing Communication Centre (DHCC), a Penn community partner, have filled that gap, frequently updating information on its social media channels and websites. Governors and mayors are more frequently using Certified Deaf Interpreters (CDI) during press briefings, and Penn alum Kate Panzer, who graduated in 2018, started a project with DHCC to sew masks with clear fronts to offer both lip-reading access and protection.

Innovative masks

Like much of the country, Panzer has stayed inside for the past several months. When the pandemic started to worsen, she temporarily left a research position in Michigan and returned to her childhood home in Media, Pennsylvania. And like many people, she wanted to give back.

At Penn, she’d taken several American Sign Language classes through the program Fisher runs, so when she read an article about a student in Kentucky making clear-fronted masks, it piqued her interest. She reached out to Fisher, who connected her with Kyle Rosenberg, DHCC’s community development and outreach coordinator.

As a volunteer, she shared her mask idea with Rosenberg. “Even in normal times, the Deaf community really struggles with clear communication,” says Rosenberg, who is himself deaf. “ASL is very visual. It relies on body language. Covering up the mouth with a mask makes communication 10 times harder.”

Rosenberg helped Panzer tweak a design and create a process to reach the community, and they took their first order on April 23. Since then, they’ve shipped about 450 masks, with a backlog of requests for hundreds more.

Though the response has been overwhelmingly positive, when constructive feedback comes in, they do take it to heart, Panzer says. For example, when mask-wearers told them that the elastic bands they’d been using rubbed uncomfortably against hearing aids, they switched to fabric ties that go around the back of the head. The masks are not medical grade, so they can’t be used in a hospital setting, but Panzer says her goal was to improve everyday interactions.

“When you can only see the eyes, it takes a lot out of expressive communication for Deaf people,” says Fisher, whose parents and one brother are deaf. “It’s really important that they be able to more fully convey facial expressions and mouth movements that influence meaning.” Masks with clear fronts help.

Continue reading at Penn Today.

Kate Panzer earned her bachelor’s degree in 2018 from the Department of Bioengineering in the School of Engineering and Applied Science at the University of Pennsylvania. She is currently a disability health and family medicine research assistant at Michigan Medicine at the University of Michigan.

NB: Kate has done prior work with ASL during her time at Penn Bioengineering. Kate’s 2018 Senior Design team created a two-way interface to help communication between deaf patients and hearing medical professionals called MEDISIGN. Fellow team members included fellow BE alumni Jackie Valeri, Nick Stiansen, and Karol Szymula. Watch their presentation on the Penn Engineering youtube channel.

June 15, 2020June 8, 2020

Lyle Ungar on Normalizing Face Masks

As scientists continue to battle the novel coronavirus, public health officials maintain that wearing a face mask is a powerful way to curb the spread of the virus and keep communities safe. However, America has struggled to adopt this change, as compared to other countries that have made wearing a face mask an unremarkable aspect of their culture.

In an opinion piece for the New York Times, Lyle Ungar, Professor of Computer and Information Science, Angela Duckworth, Rosa Lee and Egbert Chang Professor in Penn Arts & Sciences and the Wharton School, and Ezekiel J. Emanuel, Professor of Medical Ethics and Health Policy in Penn’s Perelman School of Medicine, propose a new approach to increase consistent face mask use among Americans: make wearing a mask “easy,” “understood,” and “expected.”

In their article, Ungar, Duckworth, and Emanuel make reference to communities that provided face masks free of charge for residents and note the decrease in infection in these areas. In addition, they point out how uncertainty about the necessity of face masks in the U.S. has led to public confusion which inhibits trust and use of masks. Finally, the three researchers push for a shift in social norms to embrace wearing a face mask as standard in America for the near future.

Some of Ungar’s recent research is also focused on the pandemic, including a “COVID Twitter map,” created with colleagues at the World Well-Being Project and Penn Medicine’s Center for Digital Health. Their map helps show, in real time, how people across the country perceive the virus and how it is affecting their mental health.

Read more about Ungar, Duckworth, and Emanuel’s strategy for normalizing face masks in their opinion piece for the New York Times.

Originally posted on the Penn Engineering blog.

Lyle Ungar is a Professor of Computer and Information Science (CIS) and a member of the Penn Bioengineering Graduate Group.

June 10, 2020June 12, 2020

How Penn’s Medical Device Development Course Adapted to the COVID-19 Pandemic

Though BE 472 was able to quickly pivot to an entirely online curriculum, some in-person aspects of the course were unfortunately lost. Pictured: BE 472’s Spring 2019 MedTech panel discussion with industry leaders Katherine High, MD (President of Spark Therapeutics), Lucas Rodriguez, PhD (CEO of CerSci Therapeutics), and Penn BE alumnus Brianna Wronko (CEO of Group K Diagnostics) (credit: Lauren McLeod BE 2020).

by Sophie Burkholder

Given the closing of schools in response to the coronavirus pandemic, professors teaching lab-based courses were forced to make some changes. One such course, the Department of Bioengineering’s Medical Device Development (BE 472) taught by Matthew R. Maltese, Ph.D., usually requires students to develop a medical device and learn how to lead a startup venture for it. Over the semester, students design prototypes for unmet needs in the medical device community, and then go on to learn about business-related aspects of the project, like fundraising, regulations, teamwork, and leadership. Maltese often encourages junior engineering students to take the course, in the hopes that their projects might become launchpads for their senior design projects the following year.

But with the pandemic’s interruptions to education restricting access to the lab, or even to some of the schematics for their earlier designs, Maltese’s Spring 2020 students had to re-focus on the business side of their projects.

Fortunately, the shift to online learning came late enough in the semester that most students had already come up with solid project ideas. Maltese then shifted gears to the less hands-on parts of the course. “There’s lots of elements to this course that are not focused on putting hands on hardware,” he says. “They’re focused on distilling and disseminating information about your endeavor to people that are interested.”

While some of those more hands-off assignments originally had some face-to-face aspects, like the final pitch competition, they’re also easy to transition to an online format. Maltese had students record videos of their pitches, which he notes is perhaps more akin to what they might have to do for external pitch competitions. And even though students couldn’t make their physical prototypes, Maltese says that they were all able to make virtual prototypes through CAD or other modeling software.

In his opinion, this renewed focus on out-of-lab prototype models might be a good thing for real-world experience. Investors and stakeholders often want the full picture of a device or startup before they even have to start working with physical material, for the sake of cost efficiency.

Students had already been working on their projects for a couple of months before the pandemic started to affect classes, so most of them stuck to their original ideas instead of adapting them to meet the needs of the current medical crisis. “Next year, I think we’re going to focus the class on COVID-19 ideas though,” says Maltese.

In fact, Medical Device Development will likely be one of many Penn Bioengineering courses that adapts its curriculum to the challenges the pandemic presented. “As a medical device community, a pharmaceutical community, a healthcare community, we were not ready for this,” Maltese notes, “but history teaches us that some of our greatest innovations emerge from our greatest trials.” He is excited for the future.

May 25, 2020May 21, 2020

Connecting Communities Impacted by COVID-19

Three Penn seniors combine their desire to help with their unique skill sets to create Corona Connects, an online platform that connects volunteers with organizations in need of support.

Developed by (from left) Steven Hamel from the School of Engineering and Applied Science, Megan Kyne from the Wharton School, and Hadassah Raskas from the College of Arts & Sciences, Corona Connects bridges the gap between those looking for ways to help and organizations in need of support.

by Erica K. Brockmeier

With college campuses shut due to the novel coronavirus, many students with new-found time on their hands have found themselves asking, “What can I do to help?”

To connect people with organizations that need support, three students have combined their desire to help with the skills they’ve learned both inside and outside the classroom. Developed by Penn seniors Steven Hamel from the School of Engineering and Applied Science, Megan Kyne from the Wharton School, and Hadassah Raskas from the College of Arts & Sciences, the online platform Corona Connects bridges the gap between people looking for ways to help and organizations looking for support.

After returning to her hometown of Silver Spring, Maryland, Raskas was eager to find some way to help but noticed that it was difficult to find opportunities online. With friends and colleagues voicing similar struggles, Raskas reached out to University of Maryland junior Elana Sichel and started putting together a list of organizations in need of help. Then, after reaching out on the Class of 2020 Facebook page about the project, Hamel, from Philadelphia, and Kyne, from Pittsburgh, offered their support to get an online platform up and running.

The team of students quickly realized that there was both a large number of individuals who wanted to find ways to help alongside an unprecedented level of need from numerous types of organizations. “We knew there was need, and we knew there was an availability of people, but the connection was missing, so we built Corona Connects to bridge this gap,” says Raskas.

Continue reading on Penn Today.

Steven Hamel graduated with his B.S.E. in Bioengineering and a Math minor in in 2020 and is currently pursuing a Master’s in Bioengineering.

May 18, 2020May 18, 2020

Language in Tweets Offers Insight Into Community-level Well-being

In a Q&A, researcher Lyle Ungar discusses why counties that frequently use words like ‘love’ aren’t necessarily happier, plus how techniques from this work led to a real-time COVID-19 wellness map.

By Michele W. Berger

People in different areas across the United States reacted differently to the threat of COVID-19. Some imposed strict restrictions, closing down most businesses deemed nonessential; others remained partially open.

Such regional distinctions are relatively easy to quantify, with their effects generally understandable through the lens of economic health. What’s harder to grasp is the emotional satisfaction and happiness specific to each place, a notion Penn’s World Well-Being Project has been working on for more than five years.

In 2017, the group published the WWBP Map, a free, interactive tool that displays characteristics of well-being by county based on Census data and billions of tweets. Recently, WWBP partnered with Penn Medicine’s Center for Digital Health to create a COVID map, which reveals in real time how people across the country perceive COVID-19 and how it’s affecting their mental health.

That map falls squarely in line with a paper published this week in the Proceedings of the National Academy of Sciences by computer scientist Lyle Ungar, one of the principal investigators of the World Well-Being Project, and colleagues from Stanford University, Stony Brook University, the National University of Singapore, and the University of Melbourne.

By analyzing 1.5 billion tweets and controlling for common words like “love” or “good,” which frequently get used to connote a missing aspect of someone’s life rather than a part that’s fulfilled, the researchers found they could discern subjective well-being at the county level. “We have a long history of collecting people’s language and asking people who are happier or sadder what words they use on Facebook and on Twitter,” Ungar says. “Those are mostly individual-level models. Here, we’re looking at community-level models.”

In a conversation with Penn Today, Ungar describes the latest work, plus how it’s useful in the time of COVID-19 and social distancing.

Read Ungar’s Q&A at Penn Today.

Dr. Lyle Ungar is a Professor of Computer and Information Science and a member of the Department of Bioengineering Graduate Group.

May 6, 2020April 30, 2020

David Meaney on Responding to the COVID-19 Crisis

David F. Meaney, the Senior Associate Dean of Penn Engineering and Solomon R. Pollack Professor of Bioengineering, is known for his scholarship and innovation in neuroengineering and concussion science, his leadership as former Chair of the Department of Bioengineering, and for his marshaling of interdisciplinary research between Penn Engineering and the University’s health schools.

The Penn Engineering community has sprung into action over the course of the past few weeks in response to COVID-19. Meaney shared his perspective on those efforts and the ones that will come online as the pandemic continues to unfold.

And then our campus — and world — changed.

COVID-19 is among us, in ways that we can’t exactly measure. It is among us in ways that we feel — we probably know someone that has tested positive for the virus, and others that are living with someone that is sick. And we all realize the virus will be with us for some time; the exact amount we don’t know.

Which brings up the question — what can we do to fight this pandemic? Many of us are trying to find ways to keep our connections with others vibrant and strong in the world of Zoom, Hangout, and BlueJeans. That is important. Let me also say that I can’t wait to reconnect with everyone in person, and close my laptop for a week.

But staying connected is what everyone should do. I often think about what can engineers do?

As the Senior Associate Dean, I want to let you know what I’m seeing on a quiet, but not shuttered, Penn campus. Examples of our response to the pandemic include our faculty designing personal protective equipment for health care workers, and our students, faculty and staff volunteering to assemble it. Other faculty are inventing COVID-19 test kits that can be completed at home, with the results available in less than an hour. Professors are sharing their creative mask designs with the world, for free, to make sure that we can all feel comfortable walking outside. And yet others that are collaborating to make a vaccine that will help us put COVID-19 behind us, permanently.

All of this is happening at speeds we have never seen before. Ideas move to prototypes and testing in days, not months, and to product in a week. We are not alone — our colleagues across campus are working at light speed to generate better tests, treatments, and models to fight COVID-19. This time, Nature has given us the problem. Time for us to solve it.

It’s more important than ever that we amplify one another’s voices and we want to hear from you. Learn more about Penn Engineering’s Share Your Story project here, and read entries here. You can also keep up-to-date on Penn Engineering’s pandemic response efforts here.

Originally posted on the Penn Engineering blog. Media contact Evan Lerner.

Learn more about the Department of Bioengineering’s COVID-19 projects in our recent blog post.

May 1, 2020April 29, 2020

Daniel A. Hammer and Miriam Wattenbarger to Offer Summer Course on COVID-19

As researchers hunt for a solution to the coronavirus outbreak, Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor in Bioengineering and in Chemical and Biomolecular Engineering (CBE), is bringing lessons from the fight for a vaccine to the classroom.

Hammer will offer a course on COVID-19 and the coronavirus pandemic during Penn’s Summer II session, which will be held online this year. The course will be co-taught with Miriam Wattenbarger, senior lecturer in CBE.

The course, “Biotechnology, Immunology, and COVID-19,” will culminate with a case study of the coronavirus pandemic including the types of drugs proposed and their mechanism of action, as well as the process of vaccine development.

“Obviously, the pandemic has been a life-altering event, causing an immense dislocation for everyone in our community, especially the students. Between me and Miriam, who has been trumpeting the importance of vaccines for some time in her graduate-level CBE courses, we have the expertise to inform students about this disease and how we might combat it,” says Hammer.

For more than ten years, Wattenbarger has run courses and labs focused on drug delivery and biotechnology, key elements of the vaccine development process.

“I invite both researchers and industry speakers to meet with my students,” Wattenbarger says, “so that they learn the crucial role engineers play in both vaccine development and manufacturing.”

Beyond studying the interactions between the immune system and viruses — including HIV, influenza, adenovirus and coronavirus — students will cover a variety of biotechnological techniques relevant to tracking and defending against them, including recombinant DNA technology, polymerase chain reaction, DNA sequencing, gene therapy, CRISPR-Cas9 editing, drug discovery, small molecule inhibitors, vaccines and the clinical trial process.

Students will also learn the mathematical principles used to quantify biomolecular interactions, as well as those found behind simple epidemiological models and methods for making and purifying drugs and vaccines.

“We all have to contribute in the ways that we can. Having taught biotechnology to freshmen for the past decade, this is something that I can do that can both inform and build community,” says Hammer. “Never has it been more important to have an informed and scientifically literate community that can fight this or any future pandemic.”

Originally posted on the Penn Engineering blog. Media contact Evan Lerner. For more on BE’s COVID-19 projects, read our recent blog post.